High Potassium Activation And Beta-Adrenergic Relaxation Of The Guinea Pig Taenia Coli (smooth Muscle, Calcium)

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Doctor of Philosophy (Ph.D.)


The activation of the guinea pig taenia coli by 145 mM K('+)/0 Na('+) was characterized with respect to contractility, Ca('2+) influx and the net Ca('2+) gain. The Ca('2+) influx rate was determined with a one minute pulse method and a prelabel (in PSS) technique. Both methods demonstrated a high K('+)-stimulated Ca('2+) influx during the first minute of high K('+) exposure. The prelabel technique detected about four times more Ca('2+) than did the pulsed method. Labelling of the Ca('2+) pool that contributes to the K('+)-stimulated influx was found to have a rate similar (t(, 1/2) about 40 seconds) to that for loss of Ca('2+) from the pool responsible for the phasic contraction. This rate is also similar to that for extracellular free Ca('2+) diffusion. Using the prelabel influx data, the Ca('2+) influx was found to quantitatively account for the net Ca('2+) gain induced by high K('+). D600, a Ca('2+) cannel blocker, was able to inhibit two Ca('2+) pathways that were found to be activated by high K('+) depolarization. There is a "fast" Ca('2+) channel associated with the K('+)-stimulated influx and the phasic contraction, and a "slow" channel responsible for Ca('2+) influx during the tonic contraction. Pretreatment of the quinea pig with agents that increase cAMP (isoproterenol, RO 20-1724 or dibutyryl cAMP) was able to inhibit Ca('2+) influx through the "fast", but not the "slow", Ca('2+) channels. Addition of isoproterenol or RO 20-1724 to tissues tonically contracted with high K('+) resulted in relaxation. There was no change in the Ca('2+) influx rate or net gain during relaxation. Also, RO 20-1724 was not found to have any effect on unidirectional Ca('2+) efflux. It was concluded that inhibition of Ca('2+) influx or stimulation of Ca('2+) extrusion was not responsible for the observed relaxation. The results suggest that (beta)-adrenergic relaxation is due to an intracelluar process such as Ca('2+) sequestration.


Health Sciences, Pharmacology

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